Correlation Between Peripheral White Blood Cell Counts And
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Int. J. Med. Sci. 2013, Vol. 10 758 Ivyspring International Publisher International Journal of Medical Sciences 2013; 10(6):758-765. doi: 10.7150/ijms.6155 Research Paper Correlation between Peripheral White Blood Cell Counts and Hyperglycemic Emergencies Wei Xu1,2 ,∗, Hai-feng Wu3,∗, Shao-gang Ma2,∗, Feng Bai2, Wen Hu2, Yue Jin4, Hong Liu2 1. School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China; 2. Department of Endocrinology, the Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, Jiangsu 223002, China; 3. Department of Critical Care Medicine, the Affiliated Yixing People’s Hospital of Jiangsu University, Yixing, Jiangsu 214200, China; 4. Department of Clinical Laboratory, the Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, Jiangsu 223002, China. ∗ Co-first authors. Corresponding author: Shao-gang Ma, Ph.D., M.D. Address: No. 60 South Huaihai Road, Huai'an 223002, China E-mail: [email protected] Fax/Phone: +86-517-8394 3591. © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/ licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2013.02.26; Accepted: 2013.04.10; Published: 2013.04.18 Abstract Objective: To determine the correlation between differential leukocyte counts and hypergly- cemic emergencies. Methods: Fifty patients with diabetic ketoacidosis (DKA), 50 patients with diabetic ketosis (DK), 50 non-DK diabetic patients with stable glycemic control, and 50 normal controls were enrolled. Their total and differential leukocyte counts were measured and evaluated at admission and after treatment. Results: The patients with DKA and DK had higher plasma glucose levels (20.84±6.73 mmol/L, 15.55±2.6 mmol/L, respectively) and more median leukocytes (13325/mm3 and 6595/mm3, re- spectively) and median neutrophils (11124 /mm3 and 4125/mm3, respectively) but fewer median eosinophils (28/mm3 and 72/mm3, respectively) compared to non-DK and control groups (all p < 0.05). Acute infection increased the elevating extent. The median leukocyte counts in DK and non-DK patients (6595/mm3 and 6008/mm3, respectively) were within the normal range. The counts of total leukocytes and neutrophils were significantly higher but eosinophils lower in severe DKA cases than in mild/moderate cases (p < 0.05). When the DKA and DK and infection resolved, total leukocytes and neutrophils fell, but eosinophils increased. The counts of total leukocytes, neutrophils, and monocytes were negatively correlated with arterial pH levels (r = −0.515, r = −0.510, r = −0.517, all p < 0.001, respectively) and positively correlated with plasma glucose levels (r = 0.722, r = 0.733, r = 0.632, all p < 0.05, respectively) in DKA patients. The arterial pH level was the most significant factor affecting total leukocytes in DKA (β = 0.467, p = 0.003). The diagnosis analysis showed that higher total leukocyte and neutrophil counts and lower eosinophil counts had a significant ability to reflect the presence of hyperglycemic emergencies. Conclusion: More total leukocytes and neutrophils but fewer eosinophils was significantly correlated with DKA and DK. Leukocyte counts can add valuable information to reflect the presence of hyperglycemic crisis and acute infection. Key words: Diabetic ketoacidosis, Diabetic ketosis, Leukocytes counts. 1. Introduction Diabetic ketoacidosis (DKA) is a common and diabetic ketosis (DK) have been considered a key serious complication of diabetes mellitus. DKA and clinical feature of type 1 diabetes mellitus (T1DM); http://www.medsci.org Int. J. Med. Sci. 2013, Vol. 10 759 however, increasing evidence indicates that DKA and subjects (control group) participated in the study DK are also common features of ketosis-prone type 2 (Table 1). In DKA group included eighteen T1DM and diabetes (T2DM) [1]. Most DKA patients require thirty-two ketosis-prone type 2 diabetes patients ac- timely treatment. Delays in the diagnosis of DKA can cording to the diagnosis criteria in document con- lead to an increase in the risk of advanced complica- cerned [2]. Patients with DKA had a plasma glucose tions and 30-day mortality. Patients with DKA are level > 13.90 mmol/L, a urine ketone level defined as generally poorly controlled prior to their admission, moderate to high (+ to +++), and an arterial pH value as reflected by high HbA1c levels [2]. Clinical studies < 7.30 at the time of admission. The criteria for DKA have demonstrated non-infectious systemic inflam- severity were previously developed: mild, 7.20 ≤ pH < mation in DKA patients, as shown by proinflamma- 7.30; moderate, 7.10 ≤ pH< 7.20; and severe, pH < 7.10 tory cytokines [3, 4] and increased peripheral white [10, 11]. blood cell (WBC) count [4, 5]. The participants underwent a routine medical It is interesting that both acute and chronic dia- examination. None of the subjects had heart failure, betic complications are correlated with elevated WBC hematologic disease, or liver or kidney dysfunction, count. There are studies indicating that an elevated and none of the patients were taking steroids. The WBC count, even within the normal range, is associ- DKA, DK, and non-DK patients received medical ated with both macro- and microvascular complica- treatment in the form of nutrition and insulin therapy. tions in type 2 diabetes [6]. Higher WBC counts may Patients with DKA and DK were monitored until be associated with the development of retinopathy, ketosis and acidosis resolved. albuminuria, and peripheral arterial disease [7–9]. Previous studies have paid much attention to proin- 2.2 Biochemical assays flammatory cytokines but little to the routine and re- Blood samples were collected into vacutainer liable WBC count. In addition, the WBC count is rou- tubes from the control and non-DK groups by veni- tinely detected in diabetic patients but does not re- puncture after an overnight fast. In the DKA and DK ceive attention from clinicians. groups, the blood samples were drawn at admission It should be stressed that previous studies only before the initial therapy and at the time of discharge provided the total leukocyte count without charac- from the hospital. terizing the differential leukocyte count in hypergly- Laboratory tests, including routine biochemistry cemic crises [4, 5]. The influence of DKA and DK on tests and arterial gas analysis, were performed us- the differential leukocyte count is poorly observed ing routine clinical assays in the hospital laboratory. and understood. The high imbalance and releasing Blood samples were collected for differential WBC characteristics of leukocytes in hyperglycemic emer- counts in tubes with EDTA and immediately pro- gencies need further study. To our knowledge, there cessed used a Mindray BC-5500 (Shenzhen, China) is no available study on the patterns or prognostic automatic blood counting system. The normal refer- value of leukocyte counts in patients with DKA and ence values for differential WBC counts are the fol- DK. Accordingly, we aimed to evaluate the changes of lowing: total WBCs 4000–10000/mm3, neutrophils total and differential leukocyte counts and the value 2000–7000/mm3, lymphocytes 800–4000/mm3, mon- by reflecting the severity of hyperglycemic emergen- ocytes 120–800/mm3, basophils 0–100/mm3, and eo- cies. sinophils 50–500/mm3. Glycated hemoglobin A1c (HbA1c) levels were 2. Methods measured using an HbA1c Meter from Bio-Rad La- 2.1 Patient recruitment and exclusion criteria boratories, Ltd. (Shanghai, China). The HbA1c test result was converted from percent HbA1c to HbA1c This study was carried out at the endocrinology in mmol/mol. and emergency department of two medical col- lege–affiliated hospitals from January 2010 to June 2.3 Statistical methods 2012 in accordance with the principles of the Declara- The results were expressed as the mean ± SD for tion of Helsinki (2001). Ethical approval was obtained quantitative variables with normal distributions. The from the Ethical Committees of Xuzhou Medical Col- parameters of total and differential WBC counts ac- lege and Jiangsu University. The written informed cording to distribution plots and analysis of variance consent was obtained from all of the participants. homogeneity were presented as the median and the A total of fifty consecutive patients with diabetic range (min–max). A pair-wise comparison among the ketoacidosis (DKA group), 50 patients with diabetic four groups was carried out using the Tukey and ketosis (DK group), 50 diabetic patients with a stable Kruskal-Wallis non-parametric ANOVA. Mann- condition (non-DK group), and 50 normal control Whitney U analysis was used for the two subgroups http://www.medsci.org Int. J. Med. Sci. 2013, Vol. 10 760 nonparametric test. Chi-squared tests were utilized and HbA1c: 12.64±2.95%, 11.90±2.92%, and 8.12±1.30, for the comparison of other clinical features. The cor- respectively for DKA, DK, and non-DK) than in the relations between the observed variables were ana- control group (plasma glucose: 5.12±0.21, HbA1c: lyzed by Pearson's correlation test. The risk markers 4.53±0.61%) (all p < 0.001). The glycemic variables for the diagnosis of DKA and DK were assessed by were higher in the DKA and DK groups than in the multiple logistic analysis. Receiver operating charac- non-DK group (all p < 0.05). With respect to age and teristic (ROC) curve analysis was performed to de- gender, there were no significant differences among termine the diagnostic performance of the variables. the four groups. The difference in the duration of di- Statistical analyses were conducted with SPSS 18.0 abetes did not reach statistical significance. Both the software (SPSS Inc., Chicago, IL) and MedCalc® ver- systolic and diastolic blood pressures were lower in sion 12.1.4.0. A two-tailed p value < 0.05 was consid- the DKA group and higher in the DK group than in ered statistically significant.